Tau-tubuline kinase 1 (TTBK1) is a recently discovered brain-specific protein kinase involved in tau phosphorylation at AD-related sites. A recent large study has identified significant association of two single nucleotide polymorphisms (SNPs) (rs2651206 and rs7764257) in the TTBK1 gene with late-onset Alzheimer's disease (LOAD) in Spanish. Here, we performed a case-control study to clarify whether the risk for LOAD might be influenced by these polymorphisms in a large Chinese cohort consisting of 400 patients and 388 healthy controls. The minor alleles of the rs2651206 polymorphism within TTBK1 was significantly associated with a reduced risk of LOAD (odds ratio/OR=0.69, P=0.011). Furthermore, rs2651206 polymorphism was still strongly associated with LOAD (OR=0.72, P=0.05) after adjusted for age, gender, and the apolipoprotein E (APOE) ɛ4 status. Haplotype analysis identified the TG haplotype, deriving from the two minor alleles, to decrease the risk of LOAD (OR=0.78, P=0.037). This study provides the evidence that variations in the TTBK1 gene may play an important role in the pathogenesis of sporadic LOAD in a Han Chinese population.
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